Candida glabrata, an opportunistic fungal pathogen, is the second most common cause of candidiasis in the United States, and its prevalence is increasing. C. glabrata has a number of genetic and physiological features that make it uniquely suited for studies designed to understand fungal virulence. The proposed experiments will identify novel mechanisms of fungal virulence, which will help direct drug discovery efforts to reduce mortality and morbidity from fungal infections. Phylogenetically, C. glabrata is closely related to the non-pathogenic, and well studied, yeast Saccharomyces cerevisiae. As a commensal organism and opportunistic pathogen, C. glabrata has evolved activities that assist it in colonizing the host, while S. cerevisiae, which has not experienced these selective pressures, has not. To analyze the contribution of recently evolved C. glabrata genes to virulence, computationally identified C. glabrata specific genes (Aim 1) will be assayed for their roles in virulence - first using transcription factor deletion mutants (Aim 2) and then individual C. glabrata specific gene deletion mutants (Aim 3). PUBLIC HEALTH RELEVANCE: The mechanisms by which the pathogenic fungus Candida glabrata causes infection, despite it being the second most common cause of candidiasis in the United States, are poorly understood. We will use computational, cell biological and genetic techniques to identify these mechanisms, thus uncovering novel mechanisms of fungal pathogenesis and identifying targets for future drug discovery efforts.